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Brian Hunis
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MA19 - Genomic Markers of IO Response (ID 922)
- Event: WCLC 2018
- Type: Mini Oral Abstract Session
- Track: Immunooncology
- Presentations: 1
- Moderators:
- Coordinates: 9/25/2018, 15:15 - 16:45, Room 201 BD
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MA19.06 - Blood Based Biomarkers: RNA, KRAS and PD-L1 Strongly Matching with Tissue and Showing Correlation with Clinical Responses In NSCLC Patient’s (ID 12358)
15:45 - 15:50 | Author(s): Brian Hunis
- Abstract
- Presentation
Background
Circulating cell-free tumor RNA (cfRNA) can be now safety isolated as cfDNA and used to measure changes in the tumor burden in the blood and changes in gene expression in non-small cell lung cancer (NSCLC) patients (pts). We are correlating these changes in cfRNA and PD-L1 with clinical response to therapy (chemotherapy, immunotherapy (IMMUNO) or targeted therapy) in stage IV NSCLC pts. Our group has been the first one to use cfRNA to detect PD-L1.
a9ded1e5ce5d75814730bb4caaf49419 Method
Blood was drawn from 31 pts under various treatments (tx) every 6-8 weeks, at the same time that CT scans were done. CfRNA was extracted from the resulting plasma and reverse transcribed with random hexamers to cDNA. Levels of cfRNA were quantitated by RT-qPCR and correlated with pts clinical response (CR/PR/SD/PD), as determined by CT scans.
4c3880bb027f159e801041b1021e88e8 Result
A total of 31 lung cancer pts were enrolled in a 2-year clinical study. 25 of 31 pts completed already the first two cycles of tx and had CT scans done. Of these, 6/8 pts with progressive disease (PD) showed increased (INC) levels of cfRNA, 9/13 pts with stable disease (SD) showed either no change (NC) or decreased (DEC) cfRNA, and 4/4 pts with partial response (PR) had NC or DEC cfRNA, corresponding to 76% concordance between cfRNA and clinical responses. PD-L1 expression measured in plasma cfRNA matched the tissue expression in 7/10 pts. In the one pt where PD-L1 was (-) in blood and (+) in tissue there was PD on IMMUNO. Among 8 pts treated with IMMUNO: 3/3 pts with PD showed INC PD-L1 cfRNA expression, 3/3 pts with SD had NC in negative PD-L1 status, and 2 pts with PR showed DEC PD-L1 cfRNA, corresponding to 100% correlation between PD-L1 expression levels and pt response. Of the 31 pts, 32% (10/31) harbored KRAS mutations in cfDNA. Of those with KRAS+ status by tissue-based testing, 83% matched with cfDNA results. Among KRAS+ pts, 80% (8/10) showed PD-L1 cfRNA expression in same blood draws with KRAS+ cfDNA, suggesting correlation between these cfDNA and cfRNA analyses.
8eea62084ca7e541d918e823422bd82e Conclusion
Significant association was observed between clinical response and changes in plasma cfRNA levels in NSCLC pts (76%). There was concordance between tissue- and blood-based testing in both DNA (KRAS mutations, 83%) and RNA (PD-L1 expression, 70%). While on IMMUNO levels of PD-L1 expression could be used to monitor response to immunotherapy.
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P2.15 - Treatment in the Real World - Support, Survivorship, Systems Research (Not CME Accredited Session) (ID 964)
- Event: WCLC 2018
- Type: Poster Viewing in the Exhibit Hall
- Track:
- Presentations: 1
- Moderators:
- Coordinates: 9/25/2018, 16:45 - 18:00, Exhibit Hall
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P2.15-23 - Are there Ethnic Disparities in the Clinical Outcomes of Non-Small Cell Lung Cancer Hispanic Patients Treated with Immunotherapy? (ID 12359)
16:45 - 18:00 | Author(s): Brian Hunis
- Abstract
Background
Immunotherapy outcomes in non-small cell lung cancer (NSCLC) are widely available thanks to studies that got the approval of PD-1/PD-L1 inhibitors. However a careful review of ethnicity can find that most of the studies were done in Non-Hispanic White or Asian populations. There is little known about the outcomes in Hispanics (H). It is well known that Hispanics (H) in the US seem to have a lower age-adjusted mortality in NSCLC and have a different gene expression profile than NHW with higher prevalence of EGFR mutations.
a9ded1e5ce5d75814730bb4caaf49419 Method
We reviewed clinical outcomes in 216 H pts with NSCLC stage IV treated with atezolizumab, nivolumab or pembrolizumab at 4 large cancer centers (Memorial Cancer Institute, University of Miami and Moffitt Cancer Center all of them in Florida (US), and the National Cancer Institute in Peru. These patients have failed at least one line of chemotherapy previously. All of these patients did not have actionable genes (EGFR. ALK, ROS-1). We assessed overall response rate ORR (CR+PR) as main objective and disease control rate (DCR: ORR+SD), median PFS (progression free survival) & overall survival (OS) and PFS at 6m and 12m as secondary objectives.
4c3880bb027f159e801041b1021e88e8 Result
Most of the pts were males: 116 (54%), 82% adenocarcinomas and the median age was 65 years (range: 37-88y). The ORR was 16% and the DCR that shows the clinical benefit was 67%. ORR and DCR were similar in adenocarcinomas (20%/68%) and squamous cell carcinomas (17%/64%). The progression free survival (PFS) at 6 months (m) and 12m were 80% and 56% respectively. Median PFS 14.5m and median overall survival were 19m, respectively.
8eea62084ca7e541d918e823422bd82e Conclusion
ORR for NSCLC pts treated with immunotherapy is 16% in Hispanics treated at 4 cancer centers compared to an expected 20% ORR for NHW as reported in the literature. Therefore it appears that Hispanics might not have a benefit from immunotherapy to the extent that NHWs do. We need a larger cohort and prospective studies to validate these findings.
6f8b794f3246b0c1e1780bb4d4d5dc53
